The present invention is directed to a method for treating cystic fibrosis. More specifically, the present invention is directed to a method for treating the symptoms of cystic fibrosis by administering a therapeutically effective amount of an sPLA2 inhibitor.
Cystic fibrosis is a hereditary disorder of the lungs, digestive, and reproductive systems. One in 2500 people in the general population in America are born with cystic fibrosis. It typically appears in early childhood and is a lifelong illness that generally gets more severe with age. Average life expectancy and quality of life are significantly reduced. There is no cure for cystic fibrosis at this time.
In cystic fibrosis the glands which produce mucus, saliva, and intestinal fluids do not work properly. Thick mucus in the lungs interferes with removal of pollutants and can cause breathing problems, infections, and lung damage. Thick secretions also may clog the pancreatic duct and block transfer of enzymes from the pancreas to the intestine. These enzymes help break down food so the body has proper growth and weight gain.
Males with cystic fibrosis are usually infertile and females may have reduced fertility due to thick secretions in the reproductive tract.
Major therapies for cystic fibrosis include the following:
1. gene therapy
2. breathing exercises
3. agents that degrade the high concentration of DNA in cystic fibrosis, e.g., human recombinant DNAse
4. drugs to restore salt and water balance, e.g., amiloride, triphosphite nucleotides
5. antibiotics for lung infection
6. inhaled beta-adrenergic agonists
7. pancreatic enzymes are taken with meals
U.S. Pat. No. 5,453,443 describes bis(aryloxy)alkanes as inhibitors of phopholipase A2 enzymes useful for a list of many disease states, inclusive of cystic fibrosis.
The mechanism of action for airway inflammation in cystic fibrosis remains poorly understood, but arachidonic acid may have a role (see, xe2x80x9cCystic Fibrosis Gene Mutation (dF508) is Associated with Intrinsic Abnormality in Ca2+xe2x80x94 Induced Arachiodonic Acid Release by Eoithelial Cellsxe2x80x9d by Miele, L.; Cordella-Miele, Eleonora; Xing, Mingzhao; Frizzell, R.; Mukherjee, Anil., DNA and Cell Biology, Vol 16, No. 6, 1997, Many Ann Liebert, Inc., pp. 749-759).
U.S. Pat. No. 5,654,326 describes the use of 1H-indole-3-glyoxylamide sPLA2 inhibitors to inhibit the sPLA2 mediated release of fatty acid.
Accordingly, there is a substantial need for a novel effective, and easy to administer treatment for the many symptoms of cystic fibrosis. It is therefore an object of the present invention to provide a methodology for effectively treating cystic fibrosis.
This invention is a method of alleviating the symptoms of a human afflicted with cystic fibrosis by administering a therapeutically effective amount of a selected sPLA2 inhibitor.
Is This invention is also a method of facilitating the clearance of retained pulmonary secretions in a human afflicted with cystic fibrosis.
This invention is also a method of facilitating lung mucus clearance in a human afflicted with cystic fibrosis.
This invention is also a method of inhibiting inflammation in the lungs in a human afflicted with cystic fibrosis.
This invention is also the use of sPLA2 inhibitors to reduce the complications of acute or chronic infections of the respiratory tree in a human afflicted with cystic fibrosis.
This invention is also the use of sPLA2 inhibitors for the manufacture of a medicament for the prophylactic or therapeutic treatment of a human afflicted with cystic fibrosis.